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DRUG CLASS:

TIE-2 antagonist

5ms
Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
P1, N=59, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Aug 2026 --> Dec 2024 | Trial primary completion date: Feb 2026 --> Dec 2024
Trial completion • Trial completion date • Trial primary completion date
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600K
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Keytruda (pembrolizumab) • trebananib (AMG 386)
8ms
Pembrolizumab (anti-PD-1) and AMG386 (angiopoietin-2 (Ang-2) in Patients with Advanced Solid Tumor (clinicaltrials.gov)
P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Feb 2025 --> Feb 2026
Trial completion date • Trial primary completion date
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600K
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Keytruda (pembrolizumab) • trebananib (AMG 386)
12ms
Second-line systemic treatment for metastatic colorectal cancer: A systematic review and Bayesian network meta-analysis based on RCT. (PubMed, PLoS One)
For most people, FOLFOX + Bevacizumab may be the best second-line systemic treatment regimen for mCRC. For RAS-mutant populations, FOLFIRI + Bevacizumab + Panitumumab is recommended. However, the therapeutic effect may be affected by the patient's physiological state, and clinicians should apply it based on actual conditions.
Clinical • Retrospective data • Review • Journal • Metastases
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RAS (Rat Sarcoma Virus)
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RAS mutation • RAS wild-type
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Avastin (bevacizumab) • erlotinib • 5-fluorouracil • Vectibix (panitumumab) • irinotecan • leucovorin calcium • trebananib (AMG 386)
1year
Phase Ib clinical and pharmacodynamic study of the TIE2 kinase inhibitor rebastinib with paclitaxel or eribulin in HER2-negative metastatic breast cancer. (PubMed, Clin Cancer Res)
In patients with MBC, the recommended phase 2 dose of rebastinib associated with pharmacodynamic evidence of TIE2 inhibition is either 50 or 100 mg PO BID in combination with paclitaxel or eribulin.
P1 data • PK/PD data • Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 negative
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paclitaxel • Halaven (eribulin mesylate) • rebastinib (DCC-2036)
1year
A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer. (PubMed, Cancer Immunol Res)
After development of acquired resistance, biopsy of one patient's KRAS wild-type, ERBB2 amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD1 immunotherapy combinations.
P1 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • POLE (DNA Polymerase Epsilon)
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HER-2 amplification • POLE mutation • KRAS wild-type • RAS wild-type
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Keytruda (pembrolizumab) • trebananib (AMG 386)
over1year
Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Feb 2024 --> Feb 2025
Trial completion date • Trial primary completion date • Metastases
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
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Keytruda (pembrolizumab) • trebananib (AMG 386)
almost2years
Angiopoietin-2 and the Vascular Endothelial Growth Factor Promote Migration and Invasion in Hepatocellular Carcinoma- and Intrahepatic Cholangiocarcinoma-Derived Spheroids. (PubMed, Biomedicines)
Inhibitors targeting ANG-2 (Trebananib) and the VEGF (Bevacizumab) effectively blocked the migration ability of spheroids that had been stimulated with rh-ANG-2 and rh-VEGF. Overall, our findings highlight the critical role played by ANG-2 and the VEGF in enhancing the ability of HCC- and iCCA-derived spheroids to migrate and invade, which are key processes in cancer progression.
Journal
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VEGFA (Vascular endothelial growth factor A) • CDH1 (Cadherin 1) • VIM (Vimentin) • CDH2 (Cadherin 2)
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Avastin (bevacizumab) • trebananib (AMG 386)
almost2years
Neoadjuvant trebananib plus paclitaxel-based chemotherapy for stage II/III breast cancer in the adaptively randomized I-SPY2 trial - Efficacy and biomarker discovery. (PubMed, Clin Cancer Res)
The Ang/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • CD8 (cluster of differentiation 8)
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HER-2 positive • HER-2 negative • HER-2 expression • CD8 expression
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MammaPrint
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Herceptin (trastuzumab) • paclitaxel • doxorubicin hydrochloride • cyclophosphamide • trebananib (AMG 386)
over2years
Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Feb 2023 --> Feb 2024
Trial primary completion date • Metastases
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • trebananib (AMG 386)
almost3years
Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer (clinicaltrials.gov)
P1, N=193, Completed, Mirati Therapeutics Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Apr 2022
Trial completion • Trial completion date • Metastases
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VEGFA (Vascular endothelial growth factor A)
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sitravatinib (MGCD516)
almost3years
MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Non-Squamous Non-Small Cell Lung Cancer Progressing On/After Checkpoint Inhibitor Therapy or Chemotherapy. (PubMed, J Thorac Oncol)
Sitravatinib with nivolumab had a manageable safety profile. Although ORR was not met, this combination demonstrated antitumor activity and encouraging survival in CPI-experienced patients with non-squamous NSCLC.
P2 data • Journal • Checkpoint inhibition • PD(L)-1 Biomarker
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KDR (Kinase insert domain receptor)
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Opdivo (nivolumab) • sitravatinib (MGCD516)
almost3years
Sitravatinib as a potent FLT3 inhibitor can overcome gilteritinib resistance in acute myeloid leukemia. (PubMed, Biomark Res)
Our study reveals the potential therapeutic role of sitravatinib in FLT3 mutant AML and provides an alternative inhibitor for the treatment of AML patients who are resistant to current FLT3 inhibitors.
Journal
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FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3 F691L • FLT3 expression • FLT3-ITD mutation + FLT3 F691L
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Xospata (gilteritinib) • sitravatinib (MGCD516)